Colitis in a transgenic mouse model of autoimmune uveitis may be induced by neoantigen presentation in the bowel.

Undifferentiated uveitis (intraocular inflammation, IOI) is an idiopathic sight-threatening, presumed autoimmune disease, accountable for ~ 10% of all blindness in the developed world. We have investigated the association of uveitis with inflammatory bowel disease (IBD) using a mouse model of spontaneous experimental autoimmune uveoretinitis (EAU). Mice expressing the transgene (Tg) hen egg lysozyme (HEL) in the retina crossed with 3A9 mice expressing a transgenic HEL-specific TCR spontaneously develop uveoretinitis at post-partum day (P)20/21. Double transgenic (dTg TCR/HEL) mice also spontaneously develop clinical signs of colitis at ~ P30 with diarrhoea, bowel shortening, oedema and lamina propria (LP) inflammatory cell infiltration. Single (s)Tg TCR (3A9) mice also show increased histological LP cell infiltration but no bowel shortening and diarrhoea. dTg TCR/HEL mice are profoundly lymphopenic at weaning. In addition, dTg TCR/HEL mice contain myeloid cells which express MHC Class II-HEL peptide complexes (MHCII-HEL), not only in the inflamed retina but also in the colon and have the potential for antigen presentation. In this model the lymphopenia and reduction in the absolute Treg numbers in dTg TCR/HEL mice is sufficient to initiate eye disease. We suggest that cell-associated antigen released from the inflamed eye can activate colonic HEL-specific T cells which, in a microbial micro-environment, not only cause colitis but feedback to amplify IOI.

Clean Cut (adaptive, multimodal surgical infection prevention programme) for low-resource settings: a prospective quality improvement study.

BACKGROUND: Clean Cut is an adaptive, multimodal programme to identify improvement opportunities and safety changes in surgery by enhancing outcomes surveillance, closing gaps in surgical infection prevention standards, and strengthening underlying processes of care. Surgical-site infections (SSIs) are common in low-income countries, so this study assessed a simple intervention to improve perioperative infection prevention practices in one. METHODS: Clean Cut was implemented in five hospitals in Ethiopia from August 2016 to October 2018. Compliance data were collected from the operating room focused on six key perioperative infection prevention standards. Process-mapping exercises were employed to understand barriers to compliance and identify locally driven improvement opportunities. Thirty-day outcomes were recorded on patients for whom intraoperative compliance information had been collected. RESULTS: Compliance data were collected from 2213 operations (374 at baseline and 1839 following process improvements) in 2202 patients. Follow-up was completed in 2159 patients (98·0 per cent). At baseline, perioperative teams complied with a mean of only 2·9 of the six critical perioperative infection prevention standards; following process improvement changes, compliance rose to a mean of 4·5 (P < 0·001). The relative risk of surgical infections after Clean Cut implementation was 0·65 (95 per cent c.i. 0·43 to 0·99; P = 0·043). Improved compliance with standards reduced the risk of postoperative infection by 46 per cent (relative risk 0·54, 95 per cent c.i. 0·30 to 0·97, for adherence score 3-6 versus 0-2; P = 0·038). CONCLUSION: The Clean Cut programme improved infection prevention standards to reduce SSI without infrastructure expenses or resource investments.

Low-dose 2-deoxy glucose stabilises tolerogenic dendritic cells and generates potent in vivo immunosuppressive effects.

Cell therapies for autoimmune diseases using tolerogenic dendritic cells (tolDC) have been promisingly explored. A major stumbling block has been generating stable tolDC, with low risk of converting to mature immunogenic DC (mDC), exacerbating disease. mDC induction involves a metabolic shift to lactate production from oxidative phosphorylation (OXPHOS) and ß-oxidation, the homeostatic energy source for resting DC. Inhibition of glycolysis through the administration of 2-deoxy glucose (2-DG) has been shown to prevent autoimmune disease experimentally but is not clinically feasible. We show here that treatment of mouse bone marrow-derived tolDC ex vivo with low-dose 2-DG (2.5 mM) (2-DGtolDC) induces a stable tolerogenic phenotype demonstrated by their failure to engage lactate production when challenged with mycobacterial antigen (Mtb). ~ 15% of 2-DGtolDC express low levels of MHC class II and 30% express CD86, while they are negative for CD40. 2-DGtolDC also express increased immune checkpoint molecules PDL-1 and SIRP-1α. Antigen-specific T cell proliferation is reduced in response to 2-DGtolDC in vitro. Mtb-stimulated 2-DGtolDC do not engage aerobic glycolysis but respond to challenge via increased OXPHOS. They also have decreased levels of p65 phosphorylation, with increased phosphorylation of the non-canonical p100 pathway. A stable tolDC phenotype is associated with sustained SIRP-1α phosphorylation and p85-AKT and PI3K signalling inhibition. Further, 2-DGtolDC preferentially secrete IL-10 rather than IL-12 upon Mtb-stimulation. Importantly, a single subcutaneous administration of 2-DGtolDC prevented experimental autoimmune uveoretinitis (EAU) in vivo. Inhibiting glycolysis of autologous tolDC prior to transfer may be a useful approach to providing stable tolDC therapy for autoimmune/immune-mediated diseases.

The Lifebox Surgical Headlight Project: engineering, testing, and field assessment in a resource-constrained setting.

BACKGROUND: Poor surgical lighting represents a major patient safety issue in low-income countries. This study evaluated device performance and undertook field assessment of high-quality headlights in Ethiopia to identify critical attributes that might improve safety and encourage local use. METHODS: Following an open call for submissions (December 2018 to January 2019), medical and technical (non-medical) headlights were identified for controlled specification testing on 14 prespecified parameters related to light quality/intensity, mounting and battery performance, including standardized illuminance measurements over time. The five highest-performing devices (differential illumination, colour rendering, spot size, mounting and battery duration) were distributed to eight Ethiopian surgeons working in resource-constrained facilities. Surgeons evaluated the devices in operating rooms, and in a comparative session rated each headlight in terms of performance and willingness to purchase. RESULTS: Of 25 submissions, eight headlights (6 surgical and 2 technical) met the criteria for full specification testing. Scores ranged from 8 to 12 (of 14), with differential performance in lighting, mounting and battery domains. Only two headlights met the illuminance parameters of more than 35 000 lux during initial testing, and no headlight satisfied all minimum specifications. Of the five headlights evaluated in Ethiopia, daily operation logbooks noted variability in surgeons' opinions of lighting quality (6-92 per cent) and spot size (0-92 per cent). Qualitative interviews also yielded important feedback, including preference for easy transport. Surgeons sought high quality with price sensitivity (using out-of-pocket funds) and identified the least expensive but high-functioning device as their first choice. CONCLUSION: No device satisfied all the predetermined specifications, and large price discrepancies were critical factors leading surgeons' choices. The favoured device is undergoing modification by the manufacturer based on design feedback so an affordable, high-quality surgical headlight crafted specifically for the needs of resource-constrained settings can be used to improve surgical safety.

ANTECEDENTES: Una iluminación quirúrgica deficiente conlleva importantes problemas de seguridad para los pacientes en países de bajos ingresos. En Etiopía, se evaluó el rendimiento y la capacidad de iluminar el campo quirúrgico de varias lámparas de alta calidad para identificar aspectos esenciales que podrían mejorar la seguridad y fomentar su uso local. MÉTODOS: Tras una convocatoria abierta (diciembre de 2018-enero de 2019), se identificaron lamparás médicas y técnicas (no médicas) para realizar un análisis de 14 variables previamente definidas en relación con la calidad/intensidad de la luz, montaje y rendimiento de la batería, además de mediciones estandarizadas de iluminancia a largo plazo. Los cinco dispositivos de mayor rendimiento (iluminación diferencial, reproducción del color, tamaño del foco, montaje y duración de la batería) se distribuyeron entre 8 cirujanos etíopes que trabajaban en instalaciones con recursos limitados. Los cirujanos evaluaron los dispositivos en quirófano y en sesiones comparativas calificaron el rendimiento de cada lámpara y la disposición para su compra. RESULTADOS: De las 25 propuestas presentadas, 8 lámparas (6 quirúrgicas y 2 técnicas) cumplieron los criterios para realizar las pruebas de especificación completas. Las puntuaciones oscilaron entre 8 y 12 (de un total de 14), con diferencias en los ámbitos de iluminación, montaje y batería. Solo 2 lámparas proporcionaron > 35000 lux de iluminancia durante la prueba inicial, y ninguna lámpara cumplió con todas las especificaciones mínimas. De las cinco lámparas evaluadas en Etiopía, hubo una gran variabilidad en las opiniones de los cirujanos anotadas en los registros realizados, tanto sobre la calidad de la iluminación (21-92%), como del tamaño del foco (0-92%). En las entrevistas cualitativas surgieron comentarios importantes como la preferencia por un transporte fácil. Los cirujanos buscaban la mejor calidad al precio más razonable (dado que se utilizaban fondos propios para su adquisición) e identificaron el dispositivo menos costoso pero con alto funcionamiento como primera opción. CONCLUSIÓN: El hecho de que ningún dispositivo satisfizo todas las especificaciones predeterminadas y la gran variabilidad de precios fueron los aspectos esenciales que determinaron la elección de los cirujanos. El dispositivo mejor valorado está siendo modificado por el fabricante en función de los comentarios de diseño, para lograr una lámpara quirúrgica asequible y de alta calidad diseñada específicamente para satisfacer las necesidades de entornos con recursos limitados en la mejora la seguridad quirúrgica.

The atypical chemokine receptor-2 does not alter corneal graft survival but regulates early stage of corneal graft-induced lymphangiogenesis.

PURPOSE: To re-evaluate the role of the atypical chemokine receptor-2 (ACKR2) in corneal graft rejection and investigate the effect of ACKR2 on inflammation-associated lymphangiogenesis using murine orthotopic corneal transplantation. METHODS: Corneal grafts were performed and evaluated in the settings of syngeneic, allogeneic and single antigen (HY-antigen) disparity pairings. Corneal vessels were quantified in whole mounts from WT, ACKR2-/- and F4/80-/-ACKR2-/- mice that received syngeneic or allogeneic grafts using anti-CD31 and anti-Lyve-1 antibodies. RESULTS: Syngeneic corneal grafts in WT and ACKR2-/- mice were 100% accepted. Fully histo-incompatible allogeneic grafts were rapidly rejected (100%) with similar tempo in both WT and ACKR2-/- hosts. Around 50% of single-antigen (HY) disparity grafts rejected at a slow but similar tempo (60 days) in WT and ACKR2-/- mice. Prior to grafting, F4/80-/-ACKR2-/- mice had lower baseline levels of limbal blood and lymphatic vessels compared to ACKR2-/- mice. Syngeneic grafts, but not allogeneic grafts, in ACKR2-/- and F4/80-/-ACKR2-/- mice induced higher levels of lymphatic sprouting and infiltration of Lyve-1+ cells during the early (3d) post-graft (pg) stage but lymphatic density was similar to WT grafted mice by 7d pg. CONCLUSIONS: Our results indicate that the chemokine scavenger receptor, ACKR2, has no role to play in the survival of allogeneic grafts. A minor role in regulation of lymphangiogenesis in the early stage of wound healing in syngeneic grafts is suggested, but this effect is probably masked by the more pronounced lymphangiogenic inflammatory response in allogeneic grafts. No additional effect was observed with the deletion of the resident macrophage gene, F4/80.

Low-background gamma-ray spectrometry for the international monitoring system.

PNNL has developed two low-background gamma-ray spectrometers in a new shallow underground laboratory, thereby significantly improving its ability to detect low levels of gamma-ray emitting fission or activation products in airborne particulate in samples from the IMS (International Monitoring System). The combination of cosmic veto panels, dry nitrogen gas to reduce radon and low background shielding results in a reduction of the background count rate by about a factor of 100 compared to detectors operating above ground at our laboratory.

Temporal trends and sources of variation in carbon flux from coarse woody debris in experimental forest canopy openings.

Pulses of respiration from coarse woody debris (CWD) have been observed immediately following canopy disturbances, but it is unclear how long these pulses are sustained. Several factors are known to influence carbon flux rates from CWD, but few studies have evaluated more than temperature and moisture. We experimentally manipulated forest structure in a second-growth northern hardwood forest and measured CO2 flux periodically for seven growing seasons following gap creation. We present an analysis of which factors, including the composition of the wood-decay fungal community influence CO2 flux. CO2 flux from CWD was strongly and positively related to wood temperature and varied significantly between substrate types (logs vs. stumps). For five growing seasons after treatment, the CO2 flux of stumps reached rates up to seven times higher than that of logs. CO2 flux of logs did not differ significantly between canopy-gap and closed-canopy conditions in the fourth through seventh post-treatment growing seasons. By the seventh season, the seasonal carbon flux of both logs and stumps had decreased significantly from prior years. Linear mixed models indicated the variation in the wood inhabiting fungal community composition explained a significant portion of variability in the CO2 flux along with measures of substrate conditions. CO2 flux rates were inversely related to fungal diversity, with logs hosting more species but emitting less CO2 than stumps. Overall, our results suggest that the current treatment of CWD in dynamic forest carbon models may be oversimplified, thereby hampering our ability to predict realistic carbon fluxes associated with wood decomposition.

Prevalence of malnutrition in children under five and school-age children in Milot Valley, Haiti.

OBJECTIVES: This research aims to provide child malnutrition prevalence data from Haiti's Milot Valley to inform the design and implementation of local health interventions. STUDY DESIGN: This cross-sectional study measured underweight, stunting, and wasting/thinness using international growth standards. METHODS: Anthropometric measurements (height/length and weight) were taken on a convenience sample of 358 children aged 0-14 years. Participants were recruited through door-to-door field visits at five recruitment sites in the Milot Valley, including individuals in the waiting area of the Pediatric Outpatient Clinic at Hôpital Sacré Coeur. Caregivers were asked questions about the child's health history, including past and current feeding practices. RESULTS: Combining moderate and severe forms of malnutrition, 14.8% of children under five were stunted, 15.3% were wasted, and 16.1% were underweight. Among children 5-14 years of age, 14.1% were stunted, 7.6% were thin (low body mass index (BMI)-for-age), and 14.5% were underweight. For children under five, 42% of mothers ended exclusive breastfeeding before the recommended six months. CONCLUSION: This study illustrates the local magnitude of childhood malnutrition and can serve as a resource for future child health interventions in the Milot Valley. To fight malnutrition, a multipronged, integrated approach is recommended, combining effective community outreach and monitoring, inpatient and outpatient nutrition therapy, and expanded partnerships with nutrition-related organizations in the region.

Bowman lecture on the role of inflammation in degenerative disease of the eye.

Inflammation, in the pathogenesis of many diseases previously thought to be strictly genetic, degenerative, metabolic, or endocrinologic in aetiology, has gradually entered the framework of a general mechanism of disease. This is exemplified by conditions such as Parkinson's disease, Alzheimer's disease, atherosclerosis, diabetes, and the more recently described Metabolic Syndrome. Chronic inflammatory processes have a significant, if not primary role, in ophthalmic diseases, particularly in retinal degenerative diseases. However, inflammation itself is not easy to define, and some aspects of inflammation may be beneficial, in a process described as 'para-inflammation' by Medhzitov. In contrast, the damaging effects of inflammation, mediated by pro-inflammatory macrophages through activation of the intracellular protein-signalling complexes, termed inflammasomes, are well recognised and are important therapeutic targets. In this review, the range of inflammatory processes in the eye is evaluated in the context of how these processes impact upon retinal degenerative disease, particularly diabetic retinopathy and age-related macular degeneration.

A shallow underground laboratory for low-background radiation measurements and materials development.

Pacific Northwest National Laboratory recently commissioned a new shallow underground laboratory, located at a depth of approximately 30 meters-water-equivalent. This new addition to the small class of radiation measurement laboratories located at modest underground depths houses the latest generation of custom-made, high-efficiency, low-background gamma-ray spectrometers and gas proportional counters. This paper describes the unique capabilities present in the shallow underground laboratory; these include large-scale ultra-pure materials production and a suite of radiation detection systems. Reported data characterize the degree of background reduction achieved through a combination of underground location, graded shielding, and rejection of cosmic-ray events. We conclude by presenting measurement targets and future opportunities.

The association of HIV viral load with indirect markers of liver injury.

This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV)-coinfected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs undetectable, <400 copies/mL) was associated with a 40% greater odds (OR 1.4, 95% CI: 1.1-1.9, P = 0.016) of FIB-4 > 1.45 in the HIV/HCV-coinfected group and 70% greater odds of FIB-4 > 1.45 (OR 1.7, 95% CI: 1.0-2.8; P = 0.046) in the HIV-mono-infected group. In multivariable analyses, a 1 log(10) increase in HIV RNA was associated with a median increase in FIB-4 of 12% in the HIV/HCV-coinfected group and 11% in the HIV-mono-infected group (P < 0.0001). Among the HIV/HCV-coinfected group, the elevating effect of HIV RNA on FIB-4 was strongest at low CD4 counts (P = 0.0037). Among the HIV-mono-infected group, the association between HIV RNA and FIB-4 was independent of CD4 cell counts. HIV RNA was associated with alterations in both liver enzymes and platelet counts. HIV antiretroviral therapy was not associated with any measure of liver injury examined. This study suggests that HIV may have direct, injurious effects on the liver and that HIV viral load should be considered when these indirect markers are used to assess liver function.

Image quantification for radiation dose calculations--limitations and uncertainties.

Radiation dose calculations in nuclear medicine depend on quantification of activity via planar and/or tomographic imaging methods. However, both methods have inherent limitations, and the accuracy of activity estimates varies with object size, background levels, and other variables. The goal of this study was to evaluate the limitations of quantitative imaging with planar and single photon emission computed tomography (SPECT) approaches, with a focus on activity quantification for use in calculating absorbed dose estimates for normal organs and tumors. To do this we studied a series of phantoms of varying complexity of geometry, with three radionuclides whose decay schemes varied from simple to complex. Four aqueous concentrations of 99mTc, ¹³¹I, and ¹¹¹In (74, 185, 370, and 740 kBq mL⁻¹) were placed in spheres of four different sizes in a water-filled phantom, with three different levels of activity in the surrounding water. Planar and SPECT images of the phantoms were obtained on a modern SPECT/computed tomography (CT) system. These radionuclides and concentration/background studies were repeated using a cardiac phantom and a modified torso phantom with liver and "tumor" regions containing the radionuclide concentrations and with the same varying background levels. Planar quantification was performed using the geometric mean approach, with attenuation correction (AC), and with and without scatter corrections (SC and NSC). SPECT images were reconstructed using attenuation maps (AM) for AC; scatter windows were used to perform SC during image reconstruction. For spherical sources with corrected data, good accuracy was observed (generally within ±10% of known values) for the largest sphere (11.5 mL) and for both planar and SPECT methods with 99mTc and ¹³¹I, but were poorest and deviated from known values for smaller objects, most notably for ¹¹¹In. SPECT quantification was affected by the partial volume effect in smaller objects and generally showed larger errors than the planar results in these cases for all radionuclides. For the cardiac phantom, results were the most accurate of all of the experiments for all radionuclides. Background subtraction was an important factor influencing these results. The contribution of scattered photons was important in quantification with ¹³¹I; if scatter was not accounted for, activity tended to be overestimated using planar quantification methods. For the torso phantom experiments, results show a clear underestimation of activity when compared to previous experiment with spherical sources for all radionuclides. Despite some variations that were observed as the level of background increased, the SPECT results were more consistent across different activity concentrations. Planar or SPECT quantification on state-of-the-art gamma cameras with appropriate quantitative processing can provide accuracies of better than 10% for large objects and modest target-to-background concentrations; however when smaller objects are used, in the presence of higher background, and for nuclides with more complex decay schemes, SPECT quantification methods generally produce better results.

The individual and combined influence of HIV and hepatitis C virus on dyslipidaemia in a high-risk Hispanic population.

OBJECTIVES: To assess the effects of chronic hepatitis C (HCV) and HIV infection on dyslipidaemia in a Hispanic population at high risk of insulin resistance. METHODS: We compared serum lipids and C-reactive protein (CRP) in 257 Hispanic adults including 47 HIV- mono-infected, 43 HCV-mono-infected and 59 HIV/HCV-co-infected individuals as well as 108 healthy controls. We also assessed the effect of HCV on lipid alterations associated with antiretroviral therapy (ART), and the impact of HCV and HIV on the associations among insulin resistance, triglycerides and cholesterol. RESULTS: HCV infection was associated with lower total and low-density lipoprotein (LDL) cholesterol, but not high-density lipoprotein (HDL) cholesterol or triglycerides compared with healthy controls. HIV infection was associated with higher triglycerides and lower HDL, but not total or LDL cholesterol. HCV mitigated the elevation of triglycerides associated with ART. In healthy Hispanic adults, insulin resistance was significantly correlated with higher triglycerides, CRP and lower HDL. HIV infection nullified the association of insulin resistance with triglycerides and HDL, and the association of triglycerides with LDL. HCV infection nullified the association of insulin resistance with triglycerides, HDL and CRP. CONCLUSIONS: HCV co-infection alters the profile of HIV-associated dyslipidaemia. The clinical significance of these findings for cardiovascular complications in HIV merits further study.

Privilege revisited: an evaluation of the eye's defence mechanisms.

Immune privilege has been considered for many years to be an interesting phenomenon associated with certain specialised tissues such as the eye and the brain. In recent years however, it has become clear that the active and passive mechanisms which underpin immune privilege are in fact a form of tissue-based immunological tolerance, perhaps of equal importance in providing defence against antigenic attack as the well established mechanisms based on the thymus (central tolerance) and circulating regulatory cells (peripheral tolerance). It would appear that each tissue possesses a degree of intrinsic immunological resistance which varies depending on the tissues and provides some degree of protection. In some tissues, such as the eye, this is protection from 'danger' has been developed to a high level of sophistication, but at a price. The mechanisms involved are presented in his lecture.

Use of Optomap for retinal screening within an eye casualty setting.

AIM: To compare nurse-guided Optomap retinal imaging with examination by an eye casualty officer, in detecting clinically significant peripheral retinal lesions in patients with retinal symptoms. METHODS: 219 patients presenting to eye casualty with retinal symptoms (flashing lights and floaters) were recruited. Retinal images were taken with the Optomap imaging system, and graded by an independent masked ophthalmologist. The findings from the Optomap and casualty officer were compared with a gold-standard examination with scleral indentation performed by a retinal specialist. We calculated the sensitivity and specificity of the Optomap and casualty officer. RESULTS: The final analysis included 205 eyes of 187 patients. The sensitivity of the Optomap for detecting retinal detachment (n = 7) was 100% (95% CI 59-100%), the same as the casualty officer. For retinal holes/tears (n = 18) the Optomap sensitivity was 33% (13-59%), compared with 67% (41-87%) for the casualty officer. Combining all retinal lesions (n = 52), the sensitivity was 62% (47-75%) and 73% (59-84%), with specificity 96% (92-99%) and 98% (94-100%) for the Optomap and casualty officer respectively. CONCLUSION: The Optomap detects retinal detachments successfully but, due to limitations in the optics, is not able to accurately detect retinal holes and tears.

Predictors of insulin resistance among Hispanic adults infected with or at risk of infection with the human immunodeficiency virus and hepatitis C virus.

Both the human immunodeficiency (HIV) and hepatitis C (HCV) viruses have been associated with insulin resistance (IR). However, our understanding of the prevalence of IR, the underlying mechanisms and predisposing factors is limited, particularly among minority populations. We conducted a study of 333 Hispanic adults including: 76 HIV monoinfected, 62 HCV monoinfected, 97 HIV/HCV co-infected and 98 uninfected controls with a specific focus on HCV infection and liver injury as possible predictors of IR. IR was measured using the Quantitative Insulin Sensitivity Check Index (QUICKI). The majority (55-69%) of participants in all groups had QUICKI values <0.350. Body mass index was associated with IR in all groups. Triglycerides were associated with IR in the uninfected control group only (-1.83, SE = 0.58, P = 0.0022). HCV was associated with IR in participants infected with HIV (-0.012, SE = 0.0046, P = 0.010). Liver injury, as measured by score to assess liver injury (FIB-4) score, was significantly associated with IR independently of HCV infection (-0.0035, SE = 0.0016, P = 0.027). In the HIV/HCV co-infected group, treatment with nucleoside reverse-transcriptase (RT) inhibitors plus non-nucleoside RT inhibitors (-0.021, SE = 0.080, P = 0.048), but not protease inhibitors (-0.000042, SE = 0.0082, P = 0.96) was associated with IR. HCV infection and antiretroviral agents, including nucleoside RT inhibitor plus non-nucleoside RT inhibitor treatment are contributors to IR in HIV infection. Liver injury, as measured by the FIB-4 score, is a predictor of IR independently of HCV infection.

Immune privilege or privileged immunity?

Immune privilege is a concept that has come of age. Where previously it was considered to be a passive phenomenon restricted to certain specialized tissues, it is now viewed as comprising several mechanisms, both active and passive, shared in many aspects with emerging notions of the mechanisms of peripheral tolerance. The relative degrees of immune privilege vary from tissue to tissue depending on the number and strength of each of the mechanisms contained in that tissue. Immune privilege can be generated in non-privileged sites such as the skin and allografts, and is a property of the tissue itself. We therefore propose that, in addition to canonical central and peripheral tolerance mechanisms, there is a third route whereby the organism promotes self-antigen non-reactivity centered on the specific properties of each tissue and varying accordingly (relative degrees of immune privilege). This third mechanism of inducing immunological tolerance, as it is a local tissue phenomenon, might have particular therapeutic significance, for instance in devising strategies for induction of immunity to tumors by disrupting immune privilege or in preventing graft rejection by promoting immune privilege.

Effect of short-term macrophage depletion in the development of posterior capsule opacification in rodents.

AIM: To evaluate the role of macrophages in the development of posterior capsule opacification (PCO). METHODS: For this purpose, an extracapsular lens extraction was performed in 18 consecutive Sprague-Dawley rats. Animals were treated with liposomal clodronate (Cl(2)MDP-lip-treated group, n = 10) or phosphate-buffered saline (PBS) (control group, n = 8) 1 day preoperatively and on the first day postoperatively, and sacrificed 3 days postoperatively. Masked clinical, light microscopy and immunohistochemistry studies were conducted. The Fisher exact test and randomisation test were used to assess statistically differences between groups. RESULTS: A statistically significant reduction in the number of macrophages (ED1+, ED7+, ED8+) was found in the Cl(2)MDP-lip-treated group compared with the PBS-lip-treated group (p = 0.048, p = 0.004, p = 0.027, respectively). There were no statistically significant differences with regards to the presence/absence of central opacification (p = 0.29) and capsular wrinkling (p = 0.21) as detected clinically between groups. Similarly, a qualitative evaluation of the degree of PCO with regards to lens epithelial cell (LEC) proliferation, capsular wrinkling and Soemmerring ring formation showed no statistically significance between groups (p = 0.27, p = 0.061, p = 1.0, respectively). However, a statistically significant reduction in the number of lens epithelial cells (LEC) counted in the centre of the posterior capsule was found in the Cl(2)MDP-lip-treated group (p = 0.009). CONCLUSION: Depletion of macrophages was accompanied by a reduction in LEC in the centre of the posterior capsule in rodents.